Search Results (127)

Background: This paper deals with the detection of amino acid composition of Iraqi Ocimum basilicum (basil) leaves and evaluation of the cytotoxic effects of the plant leaf extract on human colorectal cancer cells. Methods: Leaves of Ocimum basilicum were collected from Iraq in November 2024. After drying and powdering, the plant material went through cold methanol extraction. Initial phytochemical screening was conducted to identify the presence of alkaloids, flavonoids, coumarins, and terpenoids. Amino acid analysis was completed by an amino acid analyzer with fluorescence detection. The cytotoxic effect was evaluated via the MTT assay on HRT-18 cell lines. Morphological changes were further tested using dual Propidium Iodide/Acridine Orange assay fluorescent staining. Results: Seventeen amino acids were detected in the plant extract. The extract showed dose-dependent cytotoxic effects on HRT-18 cells, with significant reduction in cell viability at concentrations of more than 25 µg/mL. Morphological alterations of membrane blebbing and cell shrinkage were observed, suggesting apoptotic activity. The IC₅₀ value confirmed strong cytotoxic potential. Conclusions: The extract of Ocimum basilicum leaf cultivated in Iraq shows a rich amino acid profile and significant cytotoxic activity against colorectal cancer cells that highlights its potential effect as a natural source of anticancer compounds. Full article

The Pelargonium genus, encompassing over 280 species, remains markedly underexplored despite extensive traditional use for respiratory, gastrointestinal, and dermatological disorders. This review of aqueous, alcoholic, and hydroalcoholic extracts reveals critical research gaps: only 10 species have undergone chemical characterization, while 17 have been evaluated for biological activities. Phytochemical analysis identified 252 unique molecules across all studies, with flavonoids emerging as the predominant class (n = 108). Glycosylated derivatives demonstrated superior bioactivity profiles compared to non-glycosylated analogs. Phenolic acids (n = 43) and coumarins (n = 31) represented additional major classes. Experimental studies primarily documented antioxidant, antibacterial, and anti-inflammatory effects, with emerging evidence for antidiabetic, anticancer, and hepatoprotective activities. However, methodological heterogeneity across studies limits comparative analysis and comprehensive understanding. In silico target prediction analysis was performed on 197 high-confidence molecular structures. Glycosylated flavonols, anthocyanidins, flavones, and coumarins showed strong predicted interactions with key inflammatory targets (ALOX15, ALOX5, PTGER4, and NOS2) and metabolic regulators (GSK3A and PI4KB), providing mechanistic support for observed therapeutic effects and suggesting potential applications in chronic inflammatory and metabolic diseases. These findings underscore the substantial therapeutic potential of underexplored Pelargonium species and advocate for systematic research employing untargeted metabolomics, standardized bioassays, and compound-specific mechanistic validation to fully unlock the pharmacological potential of this diverse genus. Full article

Artocarpus heterophyllus (jackfruit) is widely distributed in subtropical and tropical regions, and some phytochemicals isolated from this species have demonstrated anti-proliferative effects. However, its impact on triple-negative breast cancer (TNBC) and HPV-related cervical cancer models remains unclear. This study evaluated the phytochemical profile and anticancer activity of an ethanolic extract from A. heterophyllus leaves (AHEE) in the TNBC cell line MDA-MB-231 and in the HPV-16⁺ murine cancer cell line TC-1. Phytochemical screening and spectroscopic analyses (UV-Vis, IR, ¹H, and ¹³C NMR) revealed the presence of tannins, alkaloids, steroids, coumarins, and flavone-type flavonoids, with a total phenolic content of 3.34 µg GAE/mg and flavonoid content of 0.44 mg QE/g extract. In 2D cultures, AHEE reduced cell viability by 49% in TC-1 and 24% in MDA-MB-231 at 300 µg/mL, inhibited colony formation and migration in TC-1, and impaired survival but not migration in MDA-MB-231. In 3D cultures, 250 µg/mL inhibited proliferation, migration, and anchorage-independent growth in both cell lines. Furthermore, the combination of AHEE with one-fifth of the IC₅₀ of doxorubicin or cisplatin produces an effect comparable to that observed with the full IC₅₀ of these drugs. These findings suggest that AHEE possesses anticancer activity with cell-type-specific effects and highlight its potential as an adjuvant therapy. Further studies are warranted to elucidate its mechanisms of action. Full article

In this paper, we will present the synthesis of coumarins bearing a phosphonate group in the C-3 position of the coumarin skeleton and phosphacoumarin derivatives. The compounds were synthesized by Knoevenagel condensation. Notably, the synthetic difficulties in preparing phosphacoumarins have limited previous studies. Our approach allows us to efficiently produce these derivatives, opening the way to investigate their biological properties. The resulting compounds were fully characterized using spectroscopic techniques and high-resolution mass spectrometry. We then evaluated the cytotoxicity of the compounds against human colon cancer HT-29 tumor and CCD 841 CoTr normal colon epithelial cells. We compared these results with coumarin activity to assess the effect of the introduction of the phosphonate group on their cytotoxicity. In addition, we performed cell cycle analysis by flow cytometry and examined the antioxidant activity of the compounds by the DPPH and FRAP methods. Furthermore, we conducted ADME analysis to gain more insight into the pharmacokinetic properties of the tested coumarins. Our study is in line with current trends in the search for new compounds with potential anticancer properties. Although there are numerous reports in the scientific literature on the anticancer activity of coumarin derivatives, the cytotoxicity of synthetic derivatives with a phosphonate group has not been investigated to date. Full article

In this study, twenty-four new furoxan and seco-coumarin hybrids were synthesized, and their antiproliferative activities against four breast cancer cells (MCF-7/ADR, MCF-7, MDA-MB-231, and MDA-MB-468) were evaluated. Among them, compound 9e exhibited significant toxicity against MCF-7/ADR cells compared to MCF-7 cells, with a 1401-fold increase, indicating its high collateral sensitivity. Meanwhile, 9e exhibited relatively lower toxicity to normal cell lines and improved solubility compared to the previous active compound, 4A93, which features a coumarin integrity core. Preliminary pharmacological studies revealed that 9e might be a potential P-glycoprotein substrate, which enters the lysosomes of MCF-7/ADR to release effective concentrations of nitric oxide, producing reactive oxygen species and inducing apoptosis. Moreover, laser confocal microscopy and Western Blot experiments showed that 9e could induce autophagy in MCF-7/ADR cells. Additionally, the anti-tumor activity of compound 9e could be inhibited by the ferroptosis inhibitor Fer-1. These results suggest that the remarkable antiproliferative potency of these hybrids in MCF-7/ADR may be related to multiple anticancer mechanisms. As a novel nitric oxide donor, compound 9e was used to explore the potential development of an anti-tumor candidate with special pharmacological mechanisms to overcome multidrug resistance in breast cancer. Full article

Osthole is a natural coumarin-like compound isolated from the Fructus cnidii. In the last few years, this plant-derived product and its derivatives have aroused much attention for their interesting biological activities, including anticancer, anti-inflammatory, neuroprotective, and insecticidal effects. This review summarizes the recent progress on the biological activities of osthole and its derivatives from 2018 to early 2025, with a focus on their total synthesis, structural modifications, and mechanisms of action. Additionally, structure–activity relationships (SARs) of osthole derivatives are presented. This review aims to serve as a comprehensive reference for future research on osthole and its derivatives in both medicinal and agricultural applications. Full article

In this study, a novel silver(I) complex [Ag(HL¹)₂]NO₃ (AgHL¹) with coumarin derivative (3E)-3-(1-{[(pyridin-2-yl)methyl]amino}ethylidene)-3,4-dihydro-2H-benzopyran-2,4-dione (HL¹) was prepared. The compounds HL¹ and AgHL¹ were characterized by IR and NMR spectroscopy, elemental analysis, and single crystal X-ray structural analysis. Specifically, the single crystal X-ray analysis determined the structures of both compounds HL¹ and AgHL¹ in their solid state, while NMR spectroscopy was used for structural determination in a solution. The HL¹ proved to be a monodentate ligand and is coordinated to the Ag(I) atom through a nitrogen atom from the 2-picolylamine fragment. In the complex AgHL¹, two molecules of neutral HL¹ are coordinated forming a nearly linear N-Ag-N arrangement. An uncoordinated nitrate anion balances the positive charge of the complex cation. NMR spectroscopy also confirmed the stability of AgHL¹ in DMSO-d₆ for 3 days. In vitro cytotoxicity of HL¹ and AgHL¹ was performed over two cancerous cell lines A549 and HT-29 and their selectivity was verified on a healthy CCD-18Co cell line. AgHL¹ exhibited low anticancer nonselective activity while the ligand was inactive. Also, the complex shows better antimicrobial activity than the positive controls on the Pseudomonas aeruginosa standard and clinical strain as well as on the tested molds. Full article

Coumarins are natural organic compounds widely found in plants that show promising anticancer properties. This article reviews the current research on the mechanisms of action of coumarins in cancer therapy, including the induction of apoptosis, inhibition of tumor cell proliferation, modulation of oxidative stress, and inhibition of angiogenesis and metastasis. Examples of coumarins with demonstrated anticancer activity, such as scopoletin, umbeliferon, esculetin and their synthetic derivatives, are also presented. The results of preclinical studies, the potential use of coumarins as stand-alone drugs and their role in combination therapy with chemotherapy are discussed. In addition, challenges related to bioavailability, safety and potential interactions with other drugs are highlighted. This review concludes by pointing out future research directions, such as the design of new coumarin analogs and the use of nanotechnology to enhance their efficacy in cancer treatment. Full article

Galium verum (Yellow Bedstraw) is a rhizomatous perennial herb belonging to the Rubiaceae family. It is native to Eurasia and Africa but has also been introduced to southern Canada and the northern U.S. Widely used in traditional medicine, G. verum has been recognized for its diuretic, anti-inflammatory, antimicrobial, analgesic, and anticancer properties. Phytochemical studies have shown that the plant is rich in significant bioactive compounds, such as flavonoids, phenolic acids, iridoids, anthraquinones, phytosterols, coumarins, and tannins. Research suggests that G. verum exhibits strong antioxidant activity, protecting cells from oxidative stress and inflammation. Its antimicrobial potential has been demonstrated against various bacterial and fungal pathogens, supporting its traditional use in wound healing and infection treatment. Moreover, modern studies indicate its cytotoxic effects on cancer cells, suggesting potential applications in oncology. Additionally, its hepatoprotective and neuroprotective properties highlight its promise for treating metabolic and neurodegenerative disorders. Despite its well-known therapeutic potential, further studies are required to fully clarify its mechanisms of action and ensure its safety for medicinal use. Given the variety of bioactive compounds found in G. verum and their pharmacological benefits, this review emphasizes the importance of this species as a valuable medicinal plant, encouraging further scientific research for its application in pharmacology. Full article

Several new coumarin–isoxazole–pyridine hybrids were synthesized through a 1,3-dipolar cycloaddition reaction of nitrile oxides, prepared in situ from pyridine aldehyde oximes, with propargyloxy- or propargylaminocoumarins in moderate-to-good yields. Synthetic modifications were applied using (diacetoxyiodo)benzene (PIDA) at room temperature, microwave irradiation, or tert-butyl nitrite (TBN) under reflux. Coumarin, isoxazole, and pyridine groups were selected for hybridization in one molecule due to their biological impact to inhibit lipid peroxidation and an enzyme implicated in inflammation. Preliminary in vitro screening tests for lipoxygenase (LOX) inhibition and anti-lipid peroxidation for the new hybrids were performed. A discussion on the structure–activity relationship is presented. Compounds 12b and 13a were found to be potent LOX inhibitors with IC₅₀ 5 μΜ and 10 μΜ, respectively, while 12b presented high (90.4%) anti-lipid peroxidation. Furthermore, hybrids 12b and 13a exhibited moderate-to-low anticancer activities on HeLa, HT-29, and H1437 cancer cells. Full article

Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes, the development of compounds with higher anticancer efficacy and a lower level of side effects is an important task in modern pharmaceutical chemistry. Herein, a mild and convenient method for the preparation of N1-substituted 3-(1,2,3-triazolyl-methoxycarbonyl)coumarins or bis(coumarine-3-carboxylate)bis(triazole)alkandiyl by the copper(I)-catalyzed Huisgen cycloaddition reaction of readily available coumarin-3-carboxylic acid propynyl ester with azides or diazides has been presented. The synthesized compounds have been tested for their cytotoxicity on various cancer and noncancerous cell lines using the MTT assay. All new compounds were nontoxic on normal epithelial VERO cells. Two derivatives exhibited selectivity towards HPV-negative human cervical cancer cells, C33 A, with excellent activities in low concentrations (GI₅₀ 4.4–7.0 µM). In vitro mechanistic studies showed that bis(coumarine)bis(triazolylester) conjugate 3 induced time-dependent apoptosis in cervical cancer cell lines C33 A and CaSki, at the GI₅₀ concentration, as measured by Annexin V-FITC/PI staining. The most active coumarin–triazolyl ester conjugate 2g possessed anticancer activities, as indicated by its ability to induce S/G2 phase cell cycle arrest at a low concentration and early apoptosis in CaSki cells. The obtained results revealed the potential of new compounds as anticancer agents, particularly against cervical cancer. Full article

Due to their remarkable biological and pharmacological activities such as antibacterial, antifungal, anticoagulant, antioxidant, anticancer, and anti-inflammatory properties, synthesis of coumarins and their derivatives has attracted considerable attention in research and development among both organic and medicinal chemists. In this paper, we demonstrated for the first time a two-step tandem enzymatic synthesis of coumarin bioamide derivatives through sustainable continuous-flow technology. Salicylaldehyde and dimethyl malonate were firstly reacted to obtain coumarin carboxylate methyl derivatives, which were then reacted with various biogenic amines at 50 °C for about 40 min under the catalysis of lipase TL IM from Thermomyces lanuginosus to obtain coumarin bioamide derivatives in continuous-flow reactors. Reaction parameters such as reaction solvent, reaction catalyst type, reactant ratio, residence time, reaction temperature and comparative experiments with traditional batch process were studied. Ideal product yields (62.7–87.1%) were obtained. Environmentally friendly methanol was applied as the reaction medium. Substantially shorter reaction times as well as a significant increase in the product yield were obtained as compared to the batch process. This innovative approach provides a promising green, efficient and rapid synthesis strategy for pharmaceutical synthesis and further research on novel coumarin bioamide derivatives. Full article

A novel series of oleanolic acid (OA, 1) derivatives incorporating phenolic and coumarin moieties were synthesized. This acid was extracted from olive pomace (Olea europaea L.) using an ultrasound-assisted method. The structures of these novel derivatives of OA were characterized through the utilization of ¹H-NMR, ¹³C-NMR and ESI-HRMS analyses. An evaluation of some biological activities of the prepared derivatives was conducted. The evaluation focused principally on the capacity of these structures to inhibit 15-lipoxygenase and α-glucosidase, as well as their anticancer properties when tested against tumour cell lines (HCT-116 and LS-174T) and a non-tumour cell line (HEK-293). In terms of their cytotoxic activity, the majority of the compounds exhibited notable inhibitory effects compared to the starting molecule, OA. Derivatives 4d, 4k and 4m exhibited particularly strong inhibitory effects against the HCT-116 cell line, with IC₅₀ values of 38.5, 39.3, 40.0 µM, respectively. Derivatives 4l, 4e and 5d demonstrated the most effective inhibition against the LS-174T cell line, with IC₅₀ values of 44.0, 44.3, 38.0 µM, respectively. However, compound 2a was the most effective, exhibiting the most potent inhibition of 15-lipoxygenase and α-glucosidase, with IC₅₀ values of 52.4 and 59.5 µM, respectively. Furthermore, molecular docking studies supported in vitro cytotoxic activity, revealing that the most potent compounds exhibited low binding energies and interacted effectively within the EGFR enzyme’s active pocket (PDB: 1M17). These findings highlight the potential of these derivatives as anticancer agents and enzymatic inhibitors, warranting further investigation. Full article

In the Mediterranean and Himalayan regions, the genus Mandragora (family Solanaceae), sometimes called mandrake, is widely utilized in herbal therapy and is well-known for its mythical associations. Objective: To compile up-to-date information on M. autumnalis’s therapeutic properties. Its pharmacological properties and phytochemical composition are particularly covered in managing several illnesses, including diabetes, cancer, and heart disease. Methods: Articles on the review topic were found by searching major scientific literature databases, such as PubMed, Scopus, ScienceDirect, SciFinder, Chemical Abstracts, and Medicinal and Aromatic Plants Abstracts. Additionally, general online searches were conducted using Google Scholar and Google. The time frame for the search included items released from 1986 to 2023. Results:Mandragora has been shown to contain a variety of phytochemicals, including coumarins, withanolides, and alkaloids. The pharmacological characteristics of M. autumnalis, such as increasing macrophage anti-inflammatory activity, free radicals inhibition, bacterial and fungal growth inhibition, cytotoxic anticancer activities in vivo and in vitro against cancer cell lines, and enzyme-inhibitory properties, are attributed to these phytochemicals. Furthermore, M. autumnalis also inhibits cholinesterase, tyrosinase, α-amylase, α-glucosidase, and free radicals. On the other hand, metabolic risk factors, including the inhibition of diabetes-causing enzymes and obesity, have been treated using dried ripe berries. Conclusions: Investigations into the pharmacological and phytochemical characteristics of M. autumnalis have revealed that this plant is a rich reservoir of new bioactive substances. This review aims to provide insight into the botanical and ecological characteristics of Mandragora autumnalis, including a summary of its phytochemical components and antioxidant, antimicrobial, antidiabetic, anticancer, enzyme-inhibitory properties, as well as toxicological implications, where its low cytotoxic activity against the normal VERO cell line has been shown. More research on this plant is necessary to ensure its efficacy and safety. Still, it is also necessary to understand the molecular mechanism of action behind the observed effects to clarify its therapeutic potential. Full article

Taraxacum officinale (dandelion) is a perennial flowering plant of the Asteraceae family that has spread globally and is well-known for its traditional uses. The aim of this work is to provide a detailed review of scientific literature on the genus Taraxacum from the last two decades, with particular emphasis on the biological and pharmacological characteristics of dandelions. The traditional use of Taraxacum species and their potential use in medicine are assessed. In addition, individual papers describing principal pathways and molecules modulated by Taraxacum in antitumoral, anti-inflammatory, antidiabetic, hepatoprotective, immunomodulatory, antimicrobial, and antioxidant activities are presented. This review of phytochemical studies reveals that dandelions contain a wide range of bioactive compounds, such as polyphenols, phytosterols, flavonoids, carotenoids, terpene, and coumarins, whose biological activities are actively explored in various areas of human health, some constituents having synergistic activities, including antioxidant, antimicrobial, anti-inflammatory and anticancer activities. The study provides a screening of Taraxacum sp. chemical composition, an assessment of the main pharmacological properties, and a description of relevant studies supporting the use of dandelion for its particularly valuable and diversified therapeutic potential in different diseases. Full article